We found that treatment of mice with IL-12p35 alone suppressed uveitis or encephalitis. In addition, adoptive transfer of ex-vivo-generated Breg cells using IL-12p35 induced expansion of Breg cells that suppressed experimental autoimmune uveitis (EAU) or experimental autoimmune encephalomyedlitis (EAE). Collectively, these studies reveal that IL-35, IL12p35 or ex-vivo generated Bregs cells can be used therapeutically to suppress uveitis and encephsalomyelitis in mice. Our discovery that IL-12p35 alone can recapitulate the immune-suppressive activities hitherto attributed to IL-35 suggest that other single chain IL-12 subunit proteins might also possess intrinsic biological activities that can be exploited therapeutically